Obesity is a growing major public health concern and is associated with various co-morbidities. Given recent evidence of increased bacterial infections in bariatric patients, morbid obesity may adversely affect the immune system. As a pleiotropic pro-inflammatory mediator produced primarily by adipocytes, leptin is a link between metabolism and immunity. Consequently, excessive leptin secretion may hinder the body's ability to defend against bacterial infection. This situation arises in morbid obesity, where chronic hyperleptinemia is observed. We used an in vivo murine model of hyperleptinemia to determine whether abnormal levels of circulating leptin have a detrimental effect on the trafficking of neutrophils, with respect to the number present, their rolling velocity, preadherence, and adherence to the endothelium. / Male CD1 background mice (6-8 weeks) were divided to 3 treatment groups receiving once daily ip injections (1) sham (PBS); (2) low leptin (1mug/g); (3) high leptin (5mug/g). After 7 days of treatment, intravital microscopy was used to visualize post-capillary venule microcirculation of the cremaster muscle in the scrotum. Parameters such as neutrophil rolling, rolling velocity, preadherence, and adherence, were recorded and measured to assess PMN kinetics. / High doses of leptin resulted in increased preadherence and adherence of neutrophils in post-capillary venules. Serum leptin and TNFalpha levels were found not to correlate with this observation; consequently, potential pathways through which leptin increases PMN adhesion could not be elucidated. Conceivably, excessive adhesion could adversely affect neutrophil trafficking by producing a shift towards the marginal pool, limiting their ability to appropriately home into bacterial targets. This could parallel the situation in morbid obesity where high concentrations of leptin are also observed.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.101709 |
| Date | January 2007 |
| Creators | Chen, Justin. |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Division of Surgical Research.) |
| Rights | © Justin Chen, 2007 |
| Relation | alephsysno: 002598626, proquestno: AAIMR32823, Theses scanned by UMI/ProQuest. |
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